Neutrophil-to-Lymphocyte Ratio Is an Independent Risk Factor for Coronary Artery Disease in Central Obesity

Several inflammatory biomarkers were found to be associated with an increased risk of cardiovascular disease. Neutrophil-to-lymphocyte ratio (NLR) is a marker of subclinical inflammation that increases with the stress response. Visceral adiposity index (VAI) calculated as a combination of anthropometric and metabolic parameters reflects both the extent and function of visceral adipose tissue. Given the association of subclinical inflammation with both obesity and cardiovascular diseases, it is plausible that the inflammation-CVD association is modulated by the amount and function of adipose tissue. Thus, our aim was to examine the association between NLR and coronary artery calcium score (CACS), an intermediate marker of coronary artery disease in asymptomatic patients across VAI tertiles. Methods: Data from 280 asymptomatic participants of a cardiovascular screening program were analysed. In addition to the collection of lifestyle and medical history, a non-contrast cardiac CT scan and laboratory tests were performed on all participants. Multivariate logistic regression was conducted with CACS > 100 as the outcome and with conventional cardiovascular risk factors and NLR, VAI, and NLR by VAI tertile as predictors. Results: We found an interaction between VAI tertiles and NLR; NLR values were similar in the lower VAI tertiles, while they were higher in the CACS > 100 in the 3rd VAI tertile (CACS ≤ 100: 1.94 ± 0.58 vs. CACS > 100: 2.48 ± 1.1, p = 0.008). According to multivariable logistic regression, the interaction between NLR and VAI tertiles remained: NLR was associated with CACS > 100 in the 3rd VAI tertile (OR = 1.67, 95% CI 1.06-2.62, p = 0.03) but not in the lower tertiles even after adjustment for age, sex, smoking, history of hypertension, hyperlipidaemia, and diabetes mellitus, as well as high-sensitivity C-reactive protein. Our findings draw attention to the independent association between subclinical, chronic, systemic inflammation and subclinical coronary disease in obesity

Impact of the COVID-19 Pandemic on Ambulatory Care Antibiotic Use in Hungary: A Population-Based Observational Study

The COVID-19 pandemic and related restrictions have potentially impacted the use of antibiotics. We aimed to analyze the use of systemic antibiotics (J01) in ambulatory care in Hungary during two pandemic years, to compare it with pre-COVID levels (January 2015–December 2019), and to describe trends based on monthly utilization. Our main findings were that during the studied COVID-19 pandemic period, compared to the pre-COVID level, an impressive 23.22% decrease in the use of systemic antibiotics was detected in ambulatory care. A significant reduction was shown in the use of several antibacterial subgroups, such as beta-lactam antibacterials, penicillins (J01C, −26.3%), and quinolones (J01M, −36.5%). The trends of antibiotic use moved in parallel with the introduction or revoking of restriction measures with a nadir in May 2020, which corresponded to a 55.46% decrease in use compared to the previous (pre-COVID) year’s monthly means. In general, the systemic antibiotic use (J01) was lower compared to the pre-COVID periods’ monthly means in almost every studied pandemic month, except for three months from September to November in 2021. The seasonal variation of antibiotic use also diminished. Active agent level analysis revealed an excessive use of azithromycin, even after evidence of ineffectiveness for COVID-19 emerged

Extracellular vesicles transmit epithelial growth factor activity in the intestinal stem cell niche.

Extracellular vesicles (EV) are membrane-surrounded vesicles that represent a novel way of intercellular communication by carrying biologically important molecules in a concentrated and protected form. The intestinal epithelium is continuously renewed by a small proliferating intestinal stem cell population (ISC), residing at the bottom of the intestinal crypts in a specific microenvironment, the stem cell niche. By using 3D mouse and human intestinal organoids, we show that intestinal fibroblast-derived EVs are involved in forming the ISC niche by transmitting Wnt and epidermal growth factor (EGF) activity. With a mouse model that expresses EGFP in the Lgr5+ ISCs we prove that loss in ISC number in the absence of EGF is prevented by fibroblast-derived EVs. Furthermore, we demonstrate that intestinal fibroblast-derived EVs carry EGF family members, such as amphiregulin. Mechanistically, blocking EV-bound amphiregulin inhibited the EV-induced survival of organoids. In contrast, EVs have no role in transporting R-Spondin, a critical niche factor amplifying Wnt signalling. Collectively, we prove the important role of fibroblast-derived EVs as a novel transmission mechanism of factors in the normal ISC niche. © AlphaMed Press 2019 SIGNIFICANCE STATEMENT: Intestinal stem cells (ISC) reside in a specific microenvironment in the intestinal epithelium, the ISC niche. Although they are critical in maintaining tissue integrity, the transmission of ISC niche factors is still not well known. Extracellular vesicles (EV) carry biologically active molecules in a membrane-surrounded form, thus, representing a novel way of intercellular communication. Here we provide evidence that fibroblast-derived EVs transport epidermal growth factor activity, one of the critical niche factors, by carrying amphiregulin, thus, they represent a novel way of intercellular signal transmission mechanism for normal ISCs

Iron uptake machinery of chloroplasts tends to utilise stoichiometric ferric-citrate complexes in Brassica napus

In plant shoots, the majority of iron is found in the chloroplasts, incorporated into the photosynthetic, sulphur assimilatory and Fe-S cluster biogenesis apparatuses. Although some members of their Fe transport machinery related to both reduction-based and nicotianamine-complex uptake systems have already been identified, the in vivo substrate preference of the system remained unknown. To clarify the mechanism of action and the substrate preference of the uptake system, intact chloroplasts of oilseed rape (Brassica napus) were subjected to Fe uptake assays using natural and artificial Fe complexes and chelates: Fe(III)-citrate 1:1.1 and 1:10, Fe(III)-malate 1:1.1, Fe(II)- and Fe(III)-nicotianamine 1:1.2, Fe(III)-EDTA 1:1 and Fe(III)-o,o’EDDHA 1:1. Iron complexes were typified by the chemical microenvironment of Fe in the compounds by Mössbauer spectroscopy. Iron uptake by chloroplasts was assessed by determining chloroplast iron content spectrophotometrically. Putative homologue genes of major, Fe uptake related, chloroplast envelope membrane proteins were identified in Brassica napus using the Brassica Database and NCBI. The expression of BnFro7 (Bra037953), BnMar1 (Bra020559), BnNico (Bra037287), BnPic1 (Bra036409), and BnYsl4 (XM_009141995.2) was studied using ß-tubulin (XM_009125342.1) and 18S rRNA (KT225373) as for reference genes in leaves subjected to chloroplast Fe uptake assays. Chloroplast inner envelope ferric chelate reductase activity of the isolated chloroplasts were also monitored using Fe(III)-EDTA. Chloroplasts preferred stoichiometric Fe(III)-citrate compared to Fe(III)-citrate 1:10 and Fe(III)-malate complexes. Moreover, uptake from Fe(III)-NA and Fe(II)-NA but also from Fe(III)-EDTA and Fe(III)-o,o’EDDHA sources were negligible (with significantly higher KM) compared to Fe(III)-citrate complexes. For these latter complexes, the light-inducible component was also missing. Regarding the components of the chloroplast Fe uptake system, genes of the reduction-based Fe uptake system showed high expression only. Nevertheless, the Fe-nicotianamine transport related chloroplast transporter BnYsl4 was mainly expressed in generative tissues. In conclusion, chloroplasts in leaves can only effectively utilize stoichiometric Fe(III)-citrate complexes in their Fe uptake. This work was supported by the grant financed by the National Research, Development and Innovation Office, Hungary (NKFIH K-124159). Á.Solti was also supported by the Bolyai János Research Scholarship of the Hungarian Academy of Sciences (BO/00207/15/4)

Az emberölés minősített esetei, valamint privilegizált esete

Próbáltam egy komplex rálátást adni szakdolgozatommal az emberölés bűntettére, kitérve a legrelevánsabb szempontokra és tulajdonságokra, így egy megfelelő összképet adni és keretbe foglalni a legsúlyosabb élet elleni bűncselekményt, az emberölést. Tíz (I.-X.) nagy fejezetet alkottam, amelyekben először a bevezetés után kitértem az emberölés társadalmi, történeti fejlődésére, egészen az ősközösségektől a szocialista államokig, illetve a mai hatályos szabályozásig. Majd bemutattam az emberölés törvényi tényállását, annak hatályos szabályozását, és a legfőbb ismertetőjegyeit, nézeteit, adatait. Ezután fejtettem ki részletesen az emberölés bűntettének kilenc minősített esetét, amelyet megpróbáltam minél több jogszabályi és eseti háttérrel megmutatni, számos Büntető Határozattal alátámasztani. Ezt követte az emberölés privilegizált esetének, az erős felindulásban elkövetett emberölésnek a bemutatása. Mindezek után az emberölés releváns alanyi és tárgyi oldalát ismertettem, mégpedig az élet elleni bűncselekmények helyét, idejét, eszközét, módját, ezt követően pedig az élet elleni bűncselekmények tetteseinek főbb személyiségjellemzőt foglaltam össze. Végezetül a befejezés következett, amelyben néhány, a dolgozatomban még nem említett információt vegyítettem a saját megítéléseimmel. Ezután friss statisztikai adatokat ismertettem, mind a befejezett emberölés, mind az emberölés kísérleti szakban maradt esetén. A dolgozat legvégén pedig az irodalomjegyzék áll, mint X. fejezet, amelyben bemutattam a felhasznált forrásaimat, mind szakirodalom, mind jogszabályi, internetes oldalon.BaN.I

A cortex sejtes és molekuláris összetétele a bursa Fabricii lymphoid follikulusaiban

A B-sejtek fejlődése madarakban a bursa Fabricii limfoid follikulusaiban zajlik. A kéregállomány szöveti szerkezete nem ismert, ennek megismerése fontos a B-sejtek fejlődésének megértésében. Eredményeink alapján a kéregállomány fejlődése a kikelés előtt megkezdődik a tenaszcin-C expresszióval egyidőben, B-sejt populációja Bu-1+/CXCR4+/IgM- és rendelkezik egy CSF1R+/TIM4+/Lep100+ makrofág populációval. In vivo és in vitro kísérleteink alapján a tenaszcin-C a B-sejtek vándorlására gátló hatású